A Predictive Model for Cytomegalovirus Infection Using Routine Hematological and Biochemical Parameters: A Pilot Study

Summary

Objective:

To examine whether hematological and biochemical parameters assist in diagnosing cytomegalovirus (CMV) infections and differentiating between CMV-G and CMV-M. Cytomegalovirus causes distinct hematological changes that can serve as markers for diagnosis.

Methods:

A retrospective analysis was conducted on 54 patients infected with CMV (25 CMV-G and 29 CMV-M) and 82 healthy controls. Age, gender, and routine hematological and biochemical parameters were evaluated. Receiver operating characteristics (ROC) analysis and logistic regression were used for data analysis.

Results:

In comparison to controls, laboratory findings of patients with CMV-G revealed characteristic decreases in red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), and platelets (p < 0.05); those with CMV-M showed reductions in the same parameters alongside elevation of monocytes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total iron-binding capacity (TIBC) and AST-to-platelet ratio index (APRI) (p < 0.05). The most effective blood markers for differentiating CMV-G patients from controls were RBC, HGB, HCT, mean corpuscular hemoglobin (MCH), platelets, AST, ferritin, APRI and Fibrosis-4 (FIB-4) meanwhile, for CMV-M patients, distinguishing markers were RBC, HGB, HCT, MCH, monocytes, platelets, AST, TIBC, APRI and FIB-4. The best predictors for distinguishing CMV-M from CMV-G were TIBC, AST, HCT, monocytes, HGB, ALT, APRI and FIB-4 all with area under the curve values greater than 0.6 (p < 0.05).

Conclusion:

Hematological and biochemical indicators can successfully distinguish CMV infections, with TIBC, AST, HCT, monocytes, HGB, ALT, APRI and FIB-4 being potentially useful for discriminating CMV-M from CMV-G. These findings could help predict CMV-infected patients.

Introduction

Cytomegalovirus (CMV) is a widespread herpesvirus that mainly affects immunocompromised individuals such as transplant recipients and neonates [1]. In serological investigations, acute and recent CMV infection is indicated by positive status for immunoglobulin (Ig)M anti-CMV antibodies (CMV-M), while previously-infected adults exhibit IgG antibodies instead (CMV-G) [2]. Notably, CMV-G antibodies are found in 60% of developed and 90% of developing countries [3]. The majority of CMV infections occur from transmission through body fluids (such as urine, saliva, and breast milk) [4]. The CMV infection does not cause obvious symptoms in adults with normal immune function; indeed, 85% to 90% of infections show no clinical symptoms [5]. Hematological parameters are important diagnostic tools by which the physiological and pathological condition of the human body can be evaluated [6]. The significance of hematological evaluation lies in its cost-effectiveness, accessibility, and predictive value, with parameters providing useful information about infections, cancer, and a variety of other diseases [6,7,8]. In addition, changes in hematological parameters reflect body function in terms of its ability to fight infections, viral or otherwise, its state of inflammation, and effects on organs [9]. Some studies have shown certain hematological abnormalities to be indicative of viral infection or disease stage, and therefore to potentially be informative in certain contexts [9,10].

Few studies have evaluated hematological parameters in children and infants with CMV infection [5,11]. Due to the fact that patients with CMV-G and CMV-M share similarities in initial symptoms and laboratory findings. In addition, hematological and biochemical alterations in CMV-G and CMV-M populations are not well-studied. This research aims to compare hematologic and biochemical parameters among patients infected with CMV and identify potential markers by which to distinguish CMV-G from CMV-M patients. In examining differences in blood profiles during viral infections, the present study contributes greatly to the regional health literature, specifically filling a gap in the assessment of hematological indices among patients affected by CMV and providing diagnostic biomarkers with potential utility in clinical practice.

Methods

This retrospective study was conducted at King Fahad Central Hospital in Kingdom of Saudi Arabia from January to December 2024. The CMV infected patients who had available hematological, biochemical and coagulation profile parameter results were included in the study. The control group comprised participants seronegative for both CMV-M and CMV-G antibodies. Individuals with previously known infectious and chronic diseases or diagnosed hepatic issues, cancer, and blood disease were excluded. A total of 54 CMV-infected patients (25 diagnosed with CMV-G, 29 with CMV-M) and 82 healthy control participants were included. Patient data such as gender, age, and hematological and biochemical results were obtained from the system (medical records). All laboratory parameters were analyzed at the clinical analysis laboratory of King Fahad Central Hospital in Jazan using automated equipment. CMV-M and CMV-G testing was performed using the enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay (ELISA) method on an EVOLIS analyzer (manufactured in Pont-de-Claix, France). Complete blood count (CBC) were performed using a Sysmex XN-2000^TM (Sysmex Corporation, Kobe, Japan). Coagulation analysis was performed with the STA Compact Max 3, which measured the prothrombin time (PT) and activated partial thromboplastin time (APTT). Chemical assays were performed with the Abbott Architect. The AST-to-platelet ratio index (AST APRI score) was calculated as (AST/upper limit of normal AST × 100/platelet count). The upper limit of normal AST was 40 U/L [12]. Age, serum aspartate transaminase (AST), platelets (PLT) and alanine transaminase (ALT) were included in the Fibrosis-4 index (FIB-4). The FIB-4 was calculated using the formula: (Age × AST) / (Platelet count × √ALT) [13].

This research was conducted in accordance with international ethical recommendations and received approval from the Jazan Ethical Committee (IRB number: No. 2532). Patient identities were protected in line with the ethical guidelines of the Jazan Ethics Committee.

Statistical analysis

Data analysis was conducted using GraphPad Prism (version 9.5.1.733, GraphPad Software, San Diego CA). Descriptive statistics were applied to analyze the data, namely mean and standard deviation. Categorical variables were analyzed and reported as frequency and percentage. One-way analysis of variance was used to compare viral infection groups (CMV-G and CMV-M) to the control group. Pearson's chi-square test or Fisher's exact test was similarly used to compare categorical variables. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value of parameters in distinguishing patients with CMV-G and CMV-M infection from healthy controls. Logistic regression analysis was conducted to determine variables connected with CMV infection, and odds ratios were determined with 95% confidence intervals for all parameters. A p-value less than 0.05 was considered statistically significant.

Results

Patient ages ranged from 3 months to 83 years. The CMV-M prevalence was highest among those <6 years (13, 44.8%), followed by the next oldest group of 6–18 years (11, 37.9%), whereas CMV-G was most common in adult patients (≥ 19 years). A statistically significant association was observed between age and type of viral infection (p < 0.001). The distribution by gender showed no significant difference (p > 0.05), with a relatively even male-to-female ratio across all groups. Across all study groups, blood group O+ was the most frequent; there was no statistically significant association of blood type with infection status (p > 0.05) (Table 1).

Table 1.

Comparison of demographic data between cmv infected patients and the control group.

Characteristics	Control) (n = 82)	CMV-G) (n = 25)	CMV-M) (n = 29)	P-Value
Age in years	N (%)	N (%)	N (%)
< 6	0 (0.0)	4 (16.0)	13 (44.8)	0.0001^
6–18	4 (4.9)	1 (4.0)	11 (37.9)
19–30	13 (15.9)	6 (24.0)	0 (0.0)
31–40	24 (29.3)	7 (28.0)	2 (6.9)
> 40	41 (50.0)	7 (28.0)	3 (10.3)
Gender
Male	38 (46.3)	12 (48.0)	14 (48.3)	0.978^
Female	44 (53.7)	13 (52.0)	15 (51.7)
Blood group
A–	1 (2.9)	0 (0.0)	0 (0.0)	0.790*
A+	10 (28.6)	2 (16.7)	1 (9.1)
AB+	1 (2.9)	0 (0.0)	0 (0.0)
B+	1 (2.9)	1 (8.3)	1 (9.1)
O–	0 (0.0)	0 (0.0)	0 (0.0)
O+	22 (62.9)	9 (75.0)	9 (81.8)

^{^}: chi square test,

^*: fisher exact test, n: total number, CMV-G: cytomegalovirus IgG, CMV-M: cytomegalovirus IgM.

Evaluation of hematological and coagulation parameters revealed red blood cell (RBC) count, hemoglobin (HGB), and hematocrit (HCT) to be significantly lower in CMV-M and CMV-G cases versus the control group (p < 0.05). The HGB and HCT were also significantly lower in CMV-M compared to CMV-G patients (p < 0.05). Meanwhile, mean corpuscular hemoglobin (MCH) was lower in CMV-M patients compared to the control group (p < 0.05), but mean corpuscular hemoglobin concentration (MCHC) was lower in CMV-G compared to CMV-M patients (p < 0.05). Platelet counts were significantly low among those with CMV-G and CMV-M compared to controls (p < 0.05). With regard to coagulation parameters, APTT was prolonged in the CMV-G infection group compared to both controls and the CMV-M group (p < 0.05), whereas PT was prolonged only in the CMV-M group compared to controls (p < 0.05). Total white blood cell (WBC) count and differential WBC counts, including lymphocyte and monocyte counts, were elevated in CMV-M patients compared to controls (p < 0.05) moreover, lymphocyte and monocyte counts were higher in CMV-M compared to CMV-G (p < 0.05). Finally, platelet/lymphocyte ratio (PLR) did not show significant difference between groups (Fig. 1).

Fig. 1.

Comparison of hematological parameters between CMV infected patients and the control group. CMV: Cytomegalovirus, RBC: Red blood cell, HGB: hemoglobin, HCT: hematocrit, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, PLT: platelet, APTT: activated partial thromboplastin time, PT: prothrombin time, WBC: White blood cell, L: lymphocyte, M: monocyte, PLR: platelets lymphocytes ratio, *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.001.

Regarding liver function, we found ALT, AST, total and conjugated bilirubin, and ferritin levels to all be higher in CMV-M patients compared to healthy controls (p < 0.05). The AST was additionally higher in CMV-M cases compared to CMV-G cases, whereas total iron-binding capacity (TIBC) was markedly lower in CMV-M compared to CMV-G and the control group (p < 0.05). We observed a significant increase in the level of the APRI score in the CMV-G and CMV-M patients in comparison to GMV negative control group. Moreover, the level of the FIB-4 showed a profound increase in CMV-G groups in compared to CMV-M and control groups (Fig. 2).

Fig. 2.

Comparison of biochemical parameters between CMV infected patients and the control group. CMV: Cytomegalovirus, ALT: alanine transaminase, AST: aspartate aminotransferase, Tot. Bil: total bilirubin, Con. Bil: conjugate bilirubin, TIBC: total iron-binding capacity, APRI: AST-to-platelet ratio index, FIB-4: Fibrosis-4 index, *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.001.

The ROC analysis was performed to identify parameters capable of distinguishing patients with CMV-G and CMV-M infection from healthy controls. The diagnostic accuracy of each parameter is reported in Table 2. Ten parameters were found able to discriminate CMV-G patients from the control group: RBC, HGB, HCT, MCH, MCHC, PLT, AST, ferritin, APRI and FIB-4 with respective area under curve (AUC) values of 0.672 (p = 0.009), 0.810 (p < 0.0001), 0.770 (p < 0.0001), 0.684 (p = 0.005), 0.640 (p = 0.034), 0.723 (p = 0.0007), 0.745 (p = 0.0009), 0.843 (p = 0.037) 0.768 (p = 0.0003) and 0.660 (p = 0.033). Meanwhile, a total of 16 parameters were identified as distinguishing CMV-M patients from controls: RBC, HGB, HCT, MCH, PLT, PT, monocyte count, PLR, ALT, AST, total bilirubin, conjugate bilirubin, TIBC, ferritin, APRI and FIB-4 with respective AUC values of 0.828 (p < 0.0001), 0.912 (p < 0.0001), 0.922 (p < 0.0001), 0.716 (p = 0.0005), 0.642 (p = 0.023), 0.710 (p = 0.013), 0.647 (p = 0.018), 0.666 (p = 0.007), 0.692 (p = 0.002), 0.878 (p < 0.0001), 0.681(p = 0.009), 0.710 (p = 0.013), 0.924 (p < 0.0001), 0.757 (p = 0.012) 0.8547 (p < 0.0001) and 0.729 (0.0007). We further evaluated whether any of the investigated parameters could distinguish CMV-G from CMV-M patients. This revealed 8 parameters to differ between the 2 infection types: HGB, HCT, MCHC, monocyte count, ALT, AST, TIBC and FIB-4, with corresponding AUCs of 0.681 (p = 0.022), 0.687 (p = 0.018), 0.659 (p = 0.045), 0.685 (p = 0.019), 0.671 (p = 0.036), 0.731 (p = 0.006), 0.800 (p = 0.006) and 0.795 (p = 0.0009).

Table 2.

Results of ROC curve analysis of hematological and biochemical parameter.

Parameter	Control vs CMV-G	Control vs CMV-M	CMV-G vs CMV-M
RBC
AUC	0.672	0.828	0.622
p -value	0.009	<0.0001	0.122
HGB
AUC	0.810	0.912	0.681
p -value	<0.0001	<0.0001	0.022
HCT
AUC	0.770	0.922	0.687
p -value	<0.0001	<0.0001	0.018
MCH
AUC	0.684	0.716	0.520
p -value	0.005	0.0005	0.801
MCHC
AUC	0.640	0.555	0.659
p -value	0.034	0.378	0.045
PLT
AUC	0.723	0.642	0.553
p -value	0.0007	0.023	0.498
PT
AUC	0.606	0.710	0.600
p -value	0.222	0.013	0.359
M
AUC	0.549	0.647	0.685
p -value	0.453	0.018	0.019
PLR
AUC	0.538	0.666	0.611
p -value	0.565	0.007	0.162
ALT
AUC	0.516	0.692	0.671
p -value	0.815	0.002	0.036
AST
AUC	0.745	0.878	0.731
p -value	0.0009	<0.0001	0.006
Tot. Bil
AUC	0.609	0.681	0.587
p -value	0.184	0.009	0.335
Con. Bil
AUC	0.606	0.710	0.600
p -value	0.222	0.013	0.359
TIBC
AUC	0.677	0.924	0.800
p -value	0.093	<0.0001	0.006
Ferritin
AUC	0.843	0.757	0.593
p -value	0.037	0.012	0.570
APRI
AUC	0.7686	0.8547	0.630
p -value	0.0003	<0.0001	0.137
FIB-4
AUC	0.660	0.729	0.795
p -value	0.033	0.0007	0.0009

ROC: receiver operating characteristics, RBC: Red blood cell, HGB: hemoglobin, HCT: hematocrit, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, PLT: platelet, PT: prothrombin time, M: monocyte, PLR: platelets lymphocytes ratio, ALT: alanine transaminase, AST: aspartate aminotransferase, Tot. Bil: total bilirubin, Con. Bil: conjugate bilirubin, TIBC: total iron-binding capacity, APRI: AST-to-platelet ratio index, FIB-4: Fibrosis-4 index, AUC: area under curve.

We next conducted logistic regression analysis to estimate the ability of the various laboratory parameters to serve as a marker differentiating CMV-M from CMV-G. A detailed analysis of the relationship between RBC, HGB, HCT, monocyte count, ALT, AST, TIBC APRI and FIB-4 and susceptibility to CMV-M compared to CMV-G infection is provided in Table 3. Parameters determined to be diagnostic factors for CMV-M infection were: HGB (odds ratio [OR] 1.30, 95% confidence level [CI] 1.02 to 1.73, p = 0.030), HCT (OR 0.90, 95% CI 0.83 to 0.97, p = 0.009), monocyte count (OR 11.24, 95% CI 1.94 to 105.6, p = 0.002), ALT (OR 1.01, 95% CI 1.00 to 1.02, p = 0.021), AST (OR 1.01, 95% CI 1.00 to 1.03, p = 0.005),TIBC (OR 0.88, 95% CI 0.79 to 0.97, p = 0.006), APRI (OR 1.58, 95% CI 1.03 to 3.76, p = 0.022) and FIB-4 (OR 0.40, 95% CI 0.16 to 0.82, p = 0.011). Thus, 1 or more of these 8 parameters may serve as an effective indicator of CMV infection.

Table 3.

Multiple logistic regression analysis of HGB, HCT, Monocyte, ALT, AST and TIBC found to be effective of differentiate of CMV-M from CMV-G infected patients.

Variable	OR(CL:95%) (CMV-M vs CMV-G)	P-value
HGB	1.30 (1.02 to 1.73)	0.030
HCT	0.90 (0.83 to 0.97)	0.009
Monocyte	11.24 (1.94 to 105.6)	0.002
ALT	1.01 (1.00 to 1.02)	0.021
AST	1.01 (1.00 to 1.03)	0.005
TIBC	0.88 (0.79 to 0.97)	0.006
APRI	1.58 (1.03 to 3.76)	0.022
FIB-4	0.40 (0.16 to 0.82)	0.011

OR: odds ratio, CL: confidence level, HGB: hemoglobin, HCT: hematocrit, ALT: alanine transaminase, AST: aspartate aminotransferase, TIBC: and total iron-binding capacity, APRI: AST-to-platelet ratio index, FIB-4: Fibrosis-4 index, CMV-G: cytomegalovirus IgG, CMV-M: cytomegalovirus IgM.

Discussion

The objective of this research was to identify parameters that can potentially predict CMV infection based on hematological and biochemical characteristics. The results highlight an important association between age and CMV infection type namely, CMV-M cases are more prevalent among children under 6 years of age, while CMV-G infections are common among adult patients. These findings are consistent with a study by Barlik et al. [14] which indicated that CMV-M antibodies are more common among young children. Correspondingly, another study demonstrated CMV-G to be more common in adults [15].

Previous work has indicated an association of CMV with anemia, and that infants with CMV infection have lower HGB values compared to controls [2,5,16]. In the current study, CMV patients exhibited significant reductions in RBC, HGB, and HCT, which parameters were determined to not only significantly predict the presence of CMV in general but also differentiate between CMV-G and CMV-M.

We further found patients with CMV to experience platelet reductions, and that platelets can serve as a potential marker for distinguishing CMV-M and CMV-G. These results are consistent with a prior report that platelets are reduced in CMV-infected patients and with the finding of Maita et al. [1] that CMV infection results in thrombocytopenia [5]. Evidence indicates that platelets contribute to innate and adaptive immune responses in various infection contexts; during CMV infections, they interact with diverse immune system cells, including neutrophils, lymphocytes, and monocytes [5,17]. It has additionally been shown that the PLR, an inflammatory marker, is associated with severe corona virus (COVID)-19 infection, and with CMV infection in young infants [5,18]. In this work, the PLR demonstrated an AUC of 0.666 (p = 0.007) in distinguishing CMV-M infection from control. The elevated APTT and PT in CMV-G patients indicate dysregulation of coagulation, potentially related to the association between CMV and thrombosis of the arterial and venous system [19].

Other discriminatory blood parameters include WBC and lymphocyte count, which were elevated in patients diagnosed with CMV-M compared to other groups. This aligns with a recent study that suggested CMV infection can cause a high white blood cell [20]. Zhan et al. [5] previously reported increased WBC, and lymphocyte counts in CMV-infected individuals compared to controls and Wang et al. [21] found CMV-infected children aged 0–6 years to have higher lymphocyte counts than control children. Our data also indicate CMV-M patients to have higher monocyte counts compared to CMV-G patients and controls, suggesting that this parameter can be used as a predictive marker for CMV infection. High monocyte count has been linked to CMV replication, with a recent review further indicating that CMV infection significantly affects numerous monocyte functions, including phagocytosis, antigen presentation, increase cytokine production, migration to infection sites, differentiation, and cytokine production; perturbation of these functions leads the body to be more susceptible to the infection [22,23]. CMV infection has also been found to affect bone marrow and cause pancytopenia, potentially explaining the associations of CMV with granulocytopenia, thrombocytopenia, and anemia [24]. Overall, WBCs may change proportion, number, and distribution in response to CMV and other viral infections, and the changes are well-mapped, making WBC count and related parameters valuable for the early diagnosis and management of such infections.

In addition to affecting blood cells, CMV infection can lead to liver injury in children, manifested as jaundice, hepatomegaly, and cholestasis [21]. Notably, pregnant women with CMV infection exhibit significantly higher AST and ALT values than their counterparts without CMV infection [10]. Linking of liver dysfunction to CMV infection has further been demonstrated, with ALT and AST showing significant association with CMV [20]. Another study found ALT and AST to be elevated in CMV patients aged from 0 day to < 1year and 0 day to < 2years [21]. The APRI and FIB-4 are non-invasive tools for assessing liver fibrosis [12,13]. The APRI score is used to estimate the risk of cirrhosis progression, and recent studies have found that a high APRI score is significantly associated with CMV infection in infants with biliary atresia (BA) [25]. The FIB-4 index, meanwhile, is used to predict significant liver fibrosis in patients with human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfection, as well as to assess the risk of developing liver cancer [26].

Collectively, these results support that CMV infection may cause liver damage. In the present work, CMV cases consistently showed significant elevation of ALT, AST, APRI and FIB-4. These parameters can also potentially differentiate CMV-M patients from both controls and the CMV-G group. Studies have shown that liver dysfunction is caused by indirect cytopathogenicity of cytotoxic T-lymphocytes, which activate cytokines and may contribute to elevated levels of these factors [27].

Another notable parameter is TIBC, which represents the accessible iron binding sites on transferrin and has been found indicative in several contexts [29,32]. That is, TIBC is associated with COVID-19 severity; and low TIBC is associated with inflammation [28,29]. In relation to CMV infection specifically, decreased TIBC has been reported in a case of extensive CMV gastroduodenitis and a case of CMV splenic infarction [30,31]. Our data further showed reduced TIBC to correlate with CMV infection, and that TIBC can differentiate between CMV-G and CMV-M patients (AUC 0.800, p = 0.006). These findings suggest that CMV infection may lead to alteration of iron metabolism; in particular, during periods of infection, damage to the liver may cause transferrin production to decrease, resulting in lower TIBC, particularly in those with a compromised immune system.

Where TIBC was reduced, ferritin levels were significantly elevated in CMV-M patients compared to the control group, and also effectively distinguished CMV patients collectively from controls. Hyperferritinemia is commonly seen in disorders driven by inflammation, and elevated ferritin was recently linked to severe cases of COVID-19 [32].

According to a recent case report, elevated ferritin in blood can be a sign of hemophagocytic lymphohistiocytosis, a serious condition associated with CMV [33]. The mechanism underlying the association of high ferritin with CMV is still unclear, 1 potential explanation is that pro-inflammatory cytokines and cellular damage may lead to increased ferritin synthesis in individuals with CMV [34].

Overall, the hematological findings in infectious diseases vary depending on whether the disease directly affects the bone marrow and whether the immune system is responding to the disease. The results of this study support that CMV significantly affects the hematopoietic system and hemostasis, causing various hematological abnormalities and hypercoagulopathy.

Study limitations

Despite the significance of these findings, this work has several limitations that should be addressed. For one, it relied on a limited sample, which may limit the generalizability of the results to other regions or populations; additional multi-center studies are required. Furthermore, medical history and laboratory values such as the presence of chronic diseases were lacking for some patients, which may impact the hematological and biochemical results. Likewise, the focus of this study on CMV excluded the influence of other viruses that may cause similar changes. Ultimately, larger, longer-term studies are needed to confirm these findings and explore other influencing factors.

In conclusion, this single-center observational study explored the utility of hematological and biochemical features as predictors capable of differentiating between CMV-M and CMV-G patients. Age was significantly associated with CMV infection type, with younger children being most affected by CMV-M while CMV-G was more common in adults. In general, CMV cases exhibited higher WBC counts and reduced RBC indices; significant alteration of liver function and inflammatory markers such as ALT, APRI, FIB-4 total bilirubin, TIBC, and serum ferritin, especially in CMV-M infections; prolonged APTT and PT, mainly in CMV-G cases; and elevated neutrophil-to-lymphocyte ratio and ferritin levels indicated strong inflammatory responses in both types of viral infection. As prospective discriminative markers, CMV-G infection was found to lead to decreases in RBC, HGB, HCT, and platelet count, whereas CMV-M infection reduced all of those parameters alongside elevating monocyte count, ALT, AST and TIBC. The ROC analysis revealed the parameters RBC, HGB, HCT, monocyte count, ALT, AST, TIBC, APRI and FIB-4 to all be effective markers for differentiating CMV-M from CMV-G patients, with significant predictive power. Our data may provide a basis for easier identification of CMV infection and differentiation between CMV-M and CMV-G infections, opening the door for categorization based on biological markers as a useful approach to determining parameter of CMV infection.

Acknowledgment

The authors extend their appreciation to the Deanship of Research and Graduate Studies at King Khalid University for funding this work through Small Research Project under grant number RGP1/168/46. This research was conducted in accordance with international ethical recommendations and received approval from the Jazan Ethical Committee (IRB number: No. 2532). Patient identities were protected in line with the ethical guidelines of the Jazan Ethics Committee. The authors would like to thank SERVICESCAPE (www.servicescape.com) for the English language editing.

Disclosure statement

Authors have no conflict of interests, and the work was not supported or funded by any drug company. We hereby confirm that the article titled has not been previously published in any preprint servers. All data collection, analysis, interpretation, and scientific writing were performed by the authors. The authors take full responsibility for the accuracy, integrity, and scientific validity of the content presented in this work.

Disclosure

This research was conducted in accordance with international ethical recommendations and received approval from the Jazan Ethical Committee (IRB number: No. 2532). Patient identities were protected in line with the ethical guidelines of the Jazan Ethics Committee. This research was funded by Deanship of Research and Graduate Studies at King Khalid University for funding this work through Small Research Project under grant number RGP1/168/46.